Developing an immunocompetent mouse model of renal cell carcinoma bone metastasis

https://openworks.mdanderson.org/sumexp23/1095/thumbnail.jp

Hypofractionated, 3-Week, Preoperative Radiotherapy for Patients With Soft Tissue Sarcomas (Hyport-Sts): A Single-Centre, Open-Label, Single-Arm, Phase 2 Trial

BACKGROUND: The standard preoperative radiotherapy regimen of 50 Gy delivered in 25 fractions for 5 weeks for soft tissue sarcomas results in excellent local control, with major wound complications occurring in approximately 35% of patients. We aimed to investigate the safety of a moderately hypofractionated, shorter regimen of radiotherapy, which could be more convenient for patients. METHODS: This single-centre, open-label, single-arm, phase 2 trial (HYPORT-STS) was done at a single tertiary cancer care centre (MD Anderson Cancer Center, Houston, TX, USA). We administered preoperative radiotherapy to a dose of 42·75 Gy in 15 fractions of 2·85 Gy/day for 3 weeks (five fractions per week) to adults (aged ≥18 years) with non-metastatic soft tissue sarcomas of the extremities or superficial trunk and an Eastern Cooperative Oncology Group performance status of 0-3. The primary endpoint was a major wound complication occurring within 120 days of surgery. Major wound complications were defined as those requiring a secondary operation, or operations, under general or regional anaesthesia for wound treatment; readmission to the hospital for wound care; invasive procedures for wound care; deep wound packing to an area of wound measuring at least 2 cm in length; prolonged dressing changes; repeat surgery for revision of a split thickness skin graft; or wet dressings for longer than 4 weeks. We analysed our primary outcome and safety in all patients who enrolled. We monitored safety using a Bayesian, one-arm, time-to-event stopping rule simulator comparing the rate of major wound complications at 120 days post-surgery among study participants with the historical rate of 35%. This trial is registered with ClinicalTrials.gov, NCT03819985, recruitment is complete, and follow-up continues. FINDINGS: Between Dec 18, 2018, and Jan 6, 2021, we assessed 157 patients for eligibility, of whom 120 were enrolled and received hypofractionated preoperative radiotherapy. At no time did the stopping rule computation indicate that the trial should be stopped early for lack of safety. Median postoperative follow-up was 24 months (IQR 17-30). Of 120 patients, 37 (31%, 95% CI 24-40) developed a major wound complication at a median time of 37 days (IQR 25-59) after surgery. No patient had acute radiation toxicity (during radiotherapy or within 4 weeks of the radiotherapy end date) of grade 3 or worse (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) or an on-treatment serious adverse event. Four (3%) of 115 patients had late radiation toxicity (≥6 months post-surgery) of at least grade 3 (CTCAE or Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme): femur fractures (n=2), lymphoedema (n=1), and skin ulceration (n=1). There were no treatment-related deaths. INTERPRETATION: Moderately hypofractionated preoperative radiotherapy delivered to patients with soft tissue sarcomas was safe and could therefore be a more convenient alternative to conventionally fractionated radiotherapy. Patients can be counselled about these results and potentially offered this regimen, particularly if it facilitates care at a sarcoma specialty centre. Results on long-term oncological, late toxicity, and functional outcomes are awaited. FUNDING: The National Cancer Institute

HIV infection and sexual risk among men who have sex with men and women (MSMW): A systematic review and meta-analysis

Objectives: To estimate the number of men who have sex with men and women who are HIV-positive in the United States, and to compare HIV prevalence rates between men who have sex with men and women, men who have sex with men only, and men who have sex with women exclusively. Methods: Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports referencing HIV prevalence and men who have sex with men and women. We searched PubMed and Ovid PsycINFO for peer-reviewed, U.S.-based articles reporting on HIV prevalence among men who have sex with men and women. We conducted event rate, effect size, moderation and sensitivity analyses. Results: We estimate that 1.0% of U.S. males are bisexually-behaving, and that 121,800 bisexually-behaving men are HIV-positive. Men who have sex with men and women are less than half as likely to be HIV-positive as men who have sex with men only (16.9% vs. 33.3%; OR = 0.41, 95% CI: 0.31, 0.54), but more than five times as likely to be HIV-positive as men who have sex with women exclusively (18.3% vs. 3.5%; OR = 5.71, 95% CI: 3.47, 9.39). They are less likely to engage in unprotected receptive anal intercourse than men who have sex with men only (15.9% vs. 35.0%; OR = 0.36, 95% CI: 0.28, 0.46). Men who have sex with men and women in samples with high racial/ethnic minority proportions had significantly higher HIV prevalence than their counterparts in low racial/ethnic minority samples. Conclusions: This represents the first meta-analysis of HIV prevalence in the U.S. between men who have sex with men and women and men who have sex with men only. Data collection, research, and HIV prevention and care delivery specifically tailored to men who have sex with men and women are necessary to better quantify and ameliorate this population's HIV burden. © 2014 Friedman et al

A mechanical model of vascular endothelium

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1993.Includes bibliographical references (leaves 208-220).by Robert L. Satcher, Jr.Ph.D

Non-radiographic Risk Factors Differentiating Atypical Lipomatous Tumors From Lipomas

Purpose: To determine non-radiographic risk factors differentiating atypical lipomatous tumors (ALTs) from lipomas.Methods: All patients with deep-seated lipomatous tumors of the extremities treated from January 2000 to October 2010 were retrospectively reviewed. Factors reviewed included age, gender, tumor location, size, histology, local recurrence, dedifferentiation and metastasis. Multivariate logistic regression models were used to evaluate the effects of patient characteristics on ALT status.Results: Ninety-four lipomas and 46 ALTs were included. Patients with an ALT were older (median: 60.5 years versus 55 years). Lipomas were evenly distributed between upper (48.9%) and lower extremities (51.1%), whereas ALTs predominately involved the lower extremities (91.3%). Median ALT size (22cm) was greater than lipomas (10cm), p<0.0001. One lipoma (1.04%) recurred at 77 months and 5 ALTs (10.9%) recurred at an average of 39 months (19 to 64 months). Two ALTs originally treated with wide resection recurred with a dedifferentiated component and were treated with wide re-excision and chemotherapy. No metastases or tumor-related deaths occurred in either group at the time of last follow-up. Patients older than 60-years, tumors greater than 10cm, or thigh location, were more likely to be diagnosed with an ALT (p<0.05).Conclusion: Lipomatous tumors were more likely to be atypical lipomatous tumors when the tumor was at least 10 cm in size, located in the thigh, or found in patients that were 60 years of age or older. These risk factors may be used to guide management and surveillance strategies when lipomatous tumors do not display characteristic radiographic features